Immunoregulation with Levamisole in Children with Frequently Relapsing Steroid Responsive Nephrotic Syndrome

ABSTRACT. The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8±3.7% and increased to normal values during therapy 34±6%; p <0.001 (control 32±5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1±5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8⁺ cells rose during levamisole therapy from 19.7±2.1 to 37±2.3 ( p <0.001), thus correcting the elevated pre-treatment OKT4⁺/OKT8⁺ ratio from 3.1±0.2 to 1.5±0.2; p <0.001 (control 1.47±0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.     

Pulse Methylprednisolone Therapy in Severe Idiopathic Childhood Nephrotic Syndrome

ABSTRACT. The effect of methyl prednisolone therapy (PM) was studied in 18 children with severe idiopathic nephrotic syndrome (NS). Eight patients were defined as "corticosteroid-resistant" because there was no response to treatment after a minimum of 4 weeks of 2 mg/kg/day of prednisone; 10 patients had a corticosteroid-dependent NS with frequent relapses which occurred under a high threshold dose of prednisone (1 mg/kg/day). Each patient received 4–6 pulses of 1 g/1.73 m² methylprednisolone. Tolerance was generally good. PM therapy permitted a more rapid remission than oral prednisone (average 9±4 days vs. 22±9 days). Remission occurred in 5 of the 8 corticosteroid-resistant patients three of these 5 patients developed corticosteroid-dependent NS. For the children with a corticosteroid-dependent nephrotic syndrome, PM therapy did not affect the threshold dose of prednisone.     

T Cell Subset and Steroid Sensitivity in Idiopathic Nephrotic Syndrome in Children

The relationship between T cell subset of peripheral blood lymphocytes and steroid sensitivity was studied in children with idiopathic nephrotic syndrome (INS). The subjects were 28 INS children, aged 2 to 16 years. T cells bearing receptors for IgG (Tγ) were identified by double rosette assay with sheep erythrocytes and IgG-sensitized ox erythrocytes. T cells bearing receptors for IgM (Tμ) were identified by IgM-sensitized ox erythrocytes rosette assay in purified T cells after incubating overnight. In steroid sensitive INS children, decreased numbers of Tγ cells and increased numbers of Tμ cells in onset or relapse were found and they were normalized with corticosteroid administration. Tγ cells of steroid nonsensitive INS children remained decreased even after steroid therapy. Tγ cells have been suggested to be, at least in part, suppressor T cells. Alteration of peripheral blood Tμ cells in this observation therefore may suggest the abnormality of suppressor T cells in INS children.     

先天性肾病综合征的治疗进展

先天性肾病综合征(CNS)通常指出生3个月内发病,临床表现符合肾病综合征(NS)(大量蛋白尿、低清蛋白血症、严重水肿和高胆固醇血症).根据病因可分为原发性(遗传性)和继发性(非遗传性),原发性因肾小球滤过屏障组成成分或足细胞发育所需调节因子相关基因突变所致;继发性因多种病原体宫内感染或母亲疾病等导致.原发性CNS的临床多表现为激素耐药性NS,激素或免疫抑制剂治疗无效,肾移植是唯一有效的治疗方式.     

The Significance of Focal Global Sclerosis in Idiopathic Nephrotic Syndrome

ABSTRACT. The clinical course of five pediatric patients with idiopathic nephrotic syndrome associated with focal global sclerosis in renal biopsy was analyzed retrospectively. The condition was defined as complete obsolescence of more than 15 % of glomeruli associated with tubular atrophy and interstitial fibrosis. At onset, all children had a steriod-sensitive relapsing nephrotic syndrome. Two became steroid-dependent and one steroid-resistent. Cyclophosphamide or chlorambucil treatment was initially followed by remission in all patients; a second course was successful in one of two patients. After 12 to 18 years of observation, four patients are in remission for periods of 2 to 12 years. Glomerular filtration rate is slightly reduced in only one patient. This study suggests that the clinical course of children with idiopathic nephrotic syndrome associated with focal global sclerosis is similar to that observed in patients with minimal glomerular changes but different from that in patients with focal segmental sclerosis.     

未变性乳清蛋白佐治单纯型肾病综合征的疗效

目的研究未变性乳清蛋白对单纯型肾病综合征(NS)的疗效及可能机制。方法将36例NS患儿随机分为2组。对照组单用泼尼松口服治疗,治疗组在激素治疗基础上加用未变性乳清蛋白治疗,随访观察1年,观察指标为复发及上呼吸道感染频率,并动态检测红细胞浆还原型谷胱甘肽(GSH)水平。结果未变性乳清蛋白可有效提高单纯性NS患儿红细胞浆GSH水平,治疗组的复发频率及上呼吸道感染频率均较对照组明显减少。结论未变性乳清蛋白可有效减少肾病复发,其机制与提高细胞GSH水平进而改善抗氧化能力有关。     

Dysfunction of the Monocyte-Macrophage System in the Idiopathic Minimal Change Nephrotic Syndrome

ABSTRACT. We studied the function of phagocytes and the distribution of lymphocyte subpopulations in 23 patients with Idiopathic Minimal Change Nephrotic Syndrome. All the patients were in relapse at the time of the study. The latter was performed before specific therapy was started. Our control group consisted of 26 normal children who were studied while undergoing routine analysis prior to plastic surgery. Polymorphonuclear leukocytes from the patients showed no alterations in their ability to ingest and to kill Candidas. On the contrary, peripheral blood monocytes had a normal phagocytic function with a decreased candidacidal activity when compared to normal controls (p<0.001). No correlation was found between serum immunoglobulin levels and the monocyte lytic function. The absolute number of B lymphocytes was significantly increased     

Thromboembolic Complications in Children with Nephrotic Syndrome

ABSTRACT. Coagulation studies were performed in 16 children with steroid responsive minimal change nephrotic syndrome in order to elucidate the incidence of thromboembolic complications. Fibrinogen and a2-macroglobulin concentrations were inversely correlated with serum albumin concentrations, antithrombin III correlated positively ( p <0.001). Factor VIII:R:AG concentration was elevated. Coagulation disturbances in children are not less severe than in adults with nephrotic syndrome. Combined scintigraphic pulmonary ventilation and perfusion studies were employed in 26 children to detect noninvasively events of pulmonary embolism, respectively their residual changes. The lung scintigraphic investigation demonstrated a pattern consistent with pulmonary embolism in 7 patients (27.9%), residual changes in 10 (38.5%) and normal findings in 9 (34.9%). The incidence of thromboembolic complications in children with severe nephrotic syndrome is as high as reported for adults. Pulmonary symptoms may well be due to pulmonary embolism.     

Genetic Basis of Congenital Nephrotic Syndrome

A young girl presented at 1 month of age with nephrotic syndrome. By incorporating clinical and pathologic data, the diagnosis of congenital nephrotic syndrome, Finnish type, was made. The differential diagnosis of early onset nephrotic syndrome, as it pertains to this patient is discussed. This article highlights recently discovered glomerular filtration proteins and their relationship to the pathophysiology of inherited kidney disease.     

遗传性肾病综合征的遗传咨询

遗传性肾病综合征指由于肾小球滤过屏障组成蛋白的编码基因或其他相关基因突变所致的肾病综合征,临床绝大多数表现为激素耐药型肾病综合征.近年来,随着分子生物学技术的匕速发展,多个与遗传性肾病综合征有关的基因被克隆、定位,这使得对多种遗传性肾病综合征进行基因诊断成为可能.而随着对遗传性肾脏疾病认识的深入和基因诊断技术的广泛开展,对此类疾病患者及家系成员提供遗传咨询也越来越有必要性,包括产前基因诊断.     

糖皮质激素受体水平在肾病综合征治疗中的意义

目的探讨糖皮质激素受体(GCR)水平对肾病综合征(NS)疗效的影响,观察绞股蓝、刺五加对GCR水平的调节作用。方法设正常对照组、治疗Ⅰ组(单用激素组)、治疗Ⅱ组(绞股蓝、刺五加与激素合用组),采用放射配体结合法分别测定各组GCR,同时观察各组同期24 h尿蛋白定量。结果与正常对照组相比,治疗Ⅰ组和Ⅱ组GCR水平均降低,治疗4周后治疗Ⅱ组不仅GCR水平恢复较治疗Ⅰ组快,且尿蛋白消退亦快。结论绞股蓝、刺五加对NS患儿GCR有调节作用,有消除尿蛋白、治疗NS的作用。     

Immunological Profile in Children with Minimal Change Nephrotic Syndrome

ABSTRACT. Peripheral blood from patients with active stage of minimal change nephrotic syndrome (MCNS) was examined for concanavalin A (ConA)-inducible suppressor T cell activity, proliferative response to phytohemagglutinin (PHA) and in the autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reaction, proportions of T cells with receptors for IgM (Tu) or IgG (Tγ) and the levels of serum immunoglobulin M, G and A. Six of 9 patients with MCNS studies showed deficiency of ConA-induced suppressor cell activity. In the AMLR, only one of 9 patients with MCNS demonstrated depressed proliferative response (p<0.05). In the allogeneic MLR, T cells from 5 of 9 patients with MCNS demonstrated poor proliferative response when stimulated with normal control non-T cells. Five of 9 patients with MCNS had depressed proliferative response to PHA. The proportion of total T cells, Tu cells and Ty cells in the patient group were comparable to healthy control group. Serum IgG was significantly decreased in 7 of 11 patients. This study demonstrates multiple immunological abnormalities in patients with MCNS that might play a role in its pathogenesis.     

Congenital Nephrotic Syndrome with adrenal calcification and cardiac malformation

Congenital Nephrotic Syndrome (CNS) with adrenal calcification and CNS with congenital heart disease (CHD) have rarely been reported. However, CNS with both these rare associations has never been previously reported. Here we report a case of CNS with both rare associations, perhaps the first report from India to the best of our knowledge.     

霉酚酸酯治疗儿童激素依赖性肾病综合征的疗效

目的观察和评价霉酚酸酯(MMF)对儿童激素依赖性肾病综合征(SDNS)的疗效及安全性。方法选取SDNS住院患儿16例。男12例,女4例;发病年龄(5.0±1.6)岁。采用MMF[25 mg/(kg.d)]联合小剂量糖皮质激素治疗,0.5年后MMF减半量,维持3个月停药。同时服用泼尼松0.5~1.0 mg/(kg.d),平均0.67 mg/(kg.d),根据病情定期减量。定期复查尿、血常规2、4 h尿蛋白定量、血清肌酐和尿素氮、肝功能,治疗3个月后进行疗效及安全性评价。结果治疗3个月后16例中完全有效13例,部分有效3例。MMF联合小剂量激素治疗前后24 h尿蛋白定量和血清清蛋白出现显著差异(P<0.01)。2例分别出现胃肠道症状和一过性白细胞减少。结论MMF是治疗儿童SDNS的一种有效、安全的免疫抑制剂。     

瘦素及可溶性瘦素受体在原发性肾病综合征患儿血脂升高中的作用

目的探讨瘦素(Leptin)及可溶性瘦素受体(sOBR)在儿童原发性肾病综合征(PNS)血脂升高中的作用。方法检测23例未经治疗的PNS患儿空腹血清血脂、血浆清蛋白、Leptin、sOBR、胰岛素及尿Leptin、sOBR水平,并与在年龄、性别、体质量指数(BMI)均匹配的15例正常儿童比较。结果肾病组血胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、载脂蛋白B(apoB)水平增高,血浆清蛋白、胰岛素水平较对照组降低。空腹血清总Leptin水平肾病组与对照组相当,而尿Leptin水平肾病组高于对照组;血清sOBR水平肾病组降低,尿sOBR水平二者无差异;血清游离Leptin指数(FLI)肾病组高于对照组。肾病组游离Leptin指数(FLI)与血浆清蛋白、HDL、apoA呈正相关,与LDL、胰岛素呈负相关。结论PNS患儿血清sOBR减少,游离瘦素增多可能为一抗高脂血症的代偿机制,但其纠正PNS脂代谢紊乱的能力并不完全。     

Left Atrial Atheromatosis in Childhood Nephrotic Syndrome

Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomenilopathy, suggesting that the “syndrome” of early onset nephrotic syndrome” progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known.     

肾病综合征脂蛋白脂酶和肝脂酶活性测定

目的探讨肾病综合征脂质代谢紊乱的发病机制。方法对62例肾病综合征和30例正常小儿测定血脂及脂蛋白脂酶和肝脂酶。结果肾病组脂蛋白脂酶及肝脂酶活性低于对照组,而胆固醇、三酰甘油、低密度脂蛋白均高于对照组。脂蛋白脂酶和肝脂酶与三酰甘油和低密度脂蛋白呈负相关。结论肾病综合征脂蛋白脂酶和肝脂酶活性降低为高三酰甘油血症的病因之一。     

An Estimation of Steroid Responsiveness of Idiopathic Nephrotic Syndrome in Iranian Children

Objective

Idiopathic Nephrotic syndrome (INS) is the most common form of nephrotic syndrome (NS) in children with the potential of progression to end stage renal disease (ESRD). INS is steroid-responsive in most children, but not all patients respond to it. The aim of this study was to determine the rate of steroid responsiveness in children with INS that referred to Children''s Medical Center since 1995 to 2007.

Methods

In as a cross sectional study, the medical records of all children with INS aged 1 to 15 years who were referred to our referral hospital was reviewed. All patients with onset of disease less than 1 year of age, spontaneous remission, secondary forms of NS associated with systemic diseases, and follow up duration of less than 12 months were excluded from the study. Patients were categorized into 6 groups: Group 1 needed biopsy prior to any treatment, group 2 non-relapsing NS, group 3 infrequently relapsing NS, Group 4 frequently relapsing NS, group 5 steroid dependent NS and group 6 steroid resistant NS.

Findings

A total of 238 patients were enrolled in the study. Kidney biopsy was performed in 79 cases. Minimal change lesion (MCL) was the most common (36.7%) pathological diagnosis. Steroid responsiveness was found in 81.5% of all cases including: 96% of MCL (consisting of biopsy proven cases and presumed ones), 32% of focal and segmental glomerulosclerosis, 73% of diffuse mesangial proliferation and 58% of membranoproliferative glomerulonephritis patients. During minimal follow up period of 12 months, there were 194 patients in remission, 32 patients with active NS, and 12 patients in ESRD.

Conclusion

Our study results showed that 81.5% of all patients, 96.2% of MCL and 32% of FSGS patients initially responded to steroid therapy.     

Comparison of Different Regimens of Prednisone Therapy in Frequently Relapsing Nephrotic Syndrome

Abstract. The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was adminstered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received a cumulative dosage of prednisone of 10 mg/m²/day and those with steroid dependency received 19 mg/m²/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75 d); however, they were significantly shorter with short-term prednisone therapy (median 33 d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.